Functional evidence of decreased tumorigenicity associated with monochromosome transfer of chromosome 14 in esophageal cancer and the mapping of tumor-suppressive regions to 14q32
Article first published online: 15 APR 2005
Copyright © 2005 Wiley-Liss, Inc.
Genes, Chromosomes and Cancer
Volume 43, Issue 3, pages 284–293, July 2005
How to Cite
Ko, J. M. Y., Yau, W. L., Chan, P. L., Lung, H. L., Yang, L., Lo, P. H. Y., Tang, J. C. O., Srivastava, G., Stanbridge, E. J. and Lung, M. L. (2005), Functional evidence of decreased tumorigenicity associated with monochromosome transfer of chromosome 14 in esophageal cancer and the mapping of tumor-suppressive regions to 14q32. Genes Chromosom. Cancer, 43: 284–293. doi: 10.1002/gcc.20190
- Issue published online: 29 APR 2005
- Article first published online: 15 APR 2005
- Manuscript Accepted: 21 FEB 2005
- Manuscript Received: 8 NOV 2004
- Research Grants Council of the Hong Kong Special Administration Region, China (HKUST). Grant Number: HKUST 6106/00M
Despite the abundant evidence of high allelic loss of chromosome arm 14q in human cancers, tumor-suppressor genes mapped to this chromosome have yet to be identified. To narrow the search for candidate genes, we performed monochromosome transfer of chromosome 14 into an esophageal carcinoma cell line, SLMT-1 S1. Statistically significant suppression of the tumorigenic potential of microcell hybrids containing the transferred chromosome 14 provided functional evidence that tumor-suppressive regions of chromosome 14 are essential for esophageal cancer. Tumor segregants emerging in nude mice during the tumorigenicity assay were analyzed by detailed PCR-microsatellite typing to identify critical nonrandomly eliminated regions (CRs). A 680-kb CR mapped to 14q32.13 and an ∼2.2-Mb CR mapped to 14q32.33 were delineated. Dual-color BAC FISH analysis of microcell hybrids and tumor segregants verified the selective loss of the 14q32.13 region. In contrast, similar transfers of an intact chromosome 11 into SLMT-1 S1 did not significantly suppress tumor formation. These functional complementation studies showing the correlation of tumorigenic potential with critical regions of chromosome 14 validated the importance of the 14q32 region in tumor suppression in esophageal cancer. The present study also paved the path for further identification of novel tumor-suppressor genes that are relevant to the molecular pathogenesis of esophageal cancer. © 2005 Wiley-Liss, Inc.